Late deterioration of renal grafts which had functioned well for several months or even years is now the major problem in studies on transplantation. Our studies will be based on the hypothesis that soluble complexes composed of transplantation antigen and antibody play a significant role in this rejection. Recently, a procedure was developed in our laboratory which is very specific and sensitive for detection and analysis of immune complexes. Studies on skin reactive transplantation antibodies that have been discovered in our laboratory will be continued with the major aim of defining the biologic role of these antibodies. In a similar fashion, the anti-N antibodies which we recently discovered in rats and which are directed against a ubiquitous rat antigen will be investigated following the hypothesis that they play a role in the prolongation of allografts. Man-mouse hybrid cells will be studied in order to detect cell-surface antigens determined by an identifiable human chromosome and obtain information about polymorphism of such antigens. Studies on the effect of presensitization of mother rats to transplantation antigen on stillbirth and neonatal mortality will be continued. Investigation on xenografts will be performed using rabbit-cat and guinea pig-rat experimental models. The major aim of this study is neutralization of natural antibodies in the recipient to the point where hyperacute rejection of the renal xenograft is prevented. BIBLIOGRAPHIC REFERENCES: Mori, S., Kano, K. and Milgrom, F.: Humoral Antibody Response in Rat Renal Allotransplantation. Transplantation 23: 128-135, 1977. Chan, M., Kano, K., Ruddle, F.H. and Milgrom, F.: Cell Surface Antigens of Man-Mouse Hybrids. Fed. Proc. 36: 1185, 1977 (Abstract).